EMA, GSK blast BMJ’s ‘flawed’ Pandemrix safety report

European drug regulatory bodies and GlaxoSmithKline have quickly rallied their rebuttals to a BMJ report that questioned the safety profile of GSK’s now-unavailable pandemic flu vaccine Pandemrix, as well as the lack of transparency over drug information.

In a report based on GSK-made internal safety reports, The BMJ found that during the 2009-2010 H1N1 flu pandemic, GSK had received 5,069 serious adverse event reports for Pandemrix in about six months. It represents a rate of 72 cases per million doses—seven times the rate for two other GSK pandemic flu vaccines combined. The report also criticized the drugmaker and health authorities for not making the information public.

By Wednesday, the European Medicines Agency (EMA), the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) and GSK had raised their issues with the article, lambasting its "scientifically inappropriate" methodology and what they saw as an "incorrect" accusation regarding transparency.

All three organizations saw the article’s method as problematic, as it relies solely on suspected adverse reactions reports received from different geographies.

The number of suspected adverse events reports submitted by the public are dependent on a myriad of factors, including the reporting system and different target populations in different regions, among others, argued Peter Arlett, the EMA’s head of pharmacovigilance and epidemiology, in his response (PDF).

"Therefore, to conclude that one product is safer than the other, based on numbers of spontaneous suspected adverse reaction reports alone, without consideration of all other relevant data, including clinical trials and epidemiological studies, is in our view ostensibly simplistic, invalid and misleading," he wrote.

GSK Vaccines’ chief medical officer, Thomas Breuer, noted that Pandemrix was mostly used in Europe, while its sister shot the BMJ used for comparison, Arepanrix, was used in Brazil, Canada, Malaysia, Mexico and Turkey. The BMJ article itself mentioned that Arepanrix was not licensed by the EMA until March 2010, at the tail of the pandemic and also near the end of the adverse events reports it used.

"As experts and regulatory authorities agree, comparing reporting rates of adverse events between products distributed across different geographies, using different surveillance systems is prone to inaccuracy and likely to result in false alerts," wrote Breuer, citing pharmacovigilance guidelines from the FDA and EMA.

An MHRA representative also pointed out that the serious events reported for Pandemrix were "much lower than the actual frequency of most common expected side effects" of a routine vaccine. He said new vaccines in the U.K. Yellow Card system tend to have a reporting rate of 1 per 1,000 doses. Compared with that, Pandemrix’s 0.072 per 1,000 rate was "extremely rare."

In terms of lack of transparency, GSK said it had turned in all safety data with health authorities, and Arlett said the agency intensified its safety monitoring of pandemic vaccines during the 2009-10 pandemic. A summary of the safety data collected and conclusions of reviews were published weekly to bi-weekly, and are still available, on its website.

Pandemrix was approved in Europe in September 2009, and its marketing authorization expired in August 2015 as GSK didn’t apply for a renewal due to post-pandemic lack of demand. The vaccine was infamously tied to some increased risk of narcolepsy in children. After analyzing scientific data examining the link, the EMA in July 2011 restricted the vaccine’s use to cases where seasonal flu shot is not available, while concluding that the benefit-risk balance of it is positive. Neither Pandemrix nor Arepanrix has been greenlighted in the U.S.

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